PACS-1 DEFINES A NOVEL GENE FAMILY OF CYTOSOLIC SORTING PROTEINS REQUIRED FOR TRANS-GOLGI NETWORK LOCALIZATION

We report the role of one member of a novel gene family, PACS-1, in th e localization of trans-Golgi network (TGN) membrane proteins. PACS-1 directs the TGN localization of furin by binding to the protease's pho sphorylated cytosolic domain. Antisense studies show TGN localization of furin and mannose-6-phosphate receptor, but not TGN46, is strictly dependent on PACS-1.Analyses in vitro and in vivo show PACS-1 has prop erties of a coat protein and connects furin to components of the clath rin-sorting machinery. Cell-free assays indicate TGN localization of f urin is directed by a PACS-1-mediated retrieval step. Together, these findings explain a mechanism by which membrane proteins in mammalian c ells are localized to the TGN.